Phosphorylcholine conjugates and corresponding antibodies

Abstract

In subjects with hypertension, increases in intima-media thickness (IMT) at four years were less in subjects also having high autoantibodies particularly IgM, to phosphorylcholine. The presence or absence of autoantibodies, particularly IgM, against phosphrylcholine is thus related to an increased or decreased risk of developing ischemic cardiovascular diseases. A method to determining antibodies, particularly IgM antibodies, toward phosphorylcholine is proposed in this invention to identify subjects at risk of developing ischemic cardiovascular diseases. Animal experiments show that medium to high levels of antibodies, particularly IgM antibodies, can be detected in plasma after active immunization with a keyhole limpet hemocyanin (KLH)-phosphorylcholine conjugate. Pharmaceutical compositions comprising a phosphorylcholine conjugate or antibody preparations, for example a monoclonal antibody, with specificity to a phosphorylcholine conjugate is proposed as is use of these compositions as active or passive immunogens in the treatment or prevention of atherosclerosis.

1 - 16 . (canceled) 
     
     
         17 . A method for assessing a human patient's risk of developing or progression of cardiovascular disease comprising:
 (a) providing phosphorylcholine (PC) conjugated to an immunologic carrier (IC),   (b) contacting said PC/IC conjugate with an antibody-containing sample from said patient,   (c) detecting antibodies from said sample complexed with PC/IC conjugate, thereby determining the level of PC/IC conjugate-reactive antibodies in sample, and   (d) diagnosing said patient as having an increased risk of developing or progression of cardiovascular disease when a low level of PC/IC conjugate-reactive antibodies is determined.   
     
     
         18 . The method of  claim 17 , wherein the cardiovascular disease is ischemic cardiovascular disease. 
     
     
         19 . The method of  claim 17 , wherein the cardiovascular disease is atherosclerosis. 
     
     
         20 . The method of  claim 17 , wherein the level of IgM antibodies from said sample complexed with the PC/IC conjugate is determined. 
     
     
         21 . The method of  claim 17 , wherein the level of IgG antibodies from said sample complexed with the PC/IC conjugate is determined. 
     
     
         22 . The method of  claim 17 , wherein the PC is linked to said IC via a spacer. 
     
     
         23 . The method of  claim 17 , wherein the IC is a protein, lipid, polymer or latex bead. 
     
     
         24 . The method of  claim 23 , wherein the protein is keyhole limpet hemocyanin (KLH) or human serum albumin (HSA). 
     
     
         25 . The method of  claim 17 , wherein the PC/IC conjugate comprises phosphorylcholine linked to a latex bead, optionally via a spacer. 
     
     
         26 . The method of  claim 17 , wherein detecting comprises an enzyme linked immunosorbent assay. 
     
     
         27 . The method of  claim 17 , wherein said patient exhibits hypertension.